Deliberate lowering of the body temperature, or “induced hypothermia”, as a therapeutic modality was first described by Talbot in 1941. (Talbot J H: The Physiologic and Therapeutic Effects of Hypothermia. N Engl J Med 224:281, 1941). The National Academy of Sciences published the investigational report on the physiological effects of hypothermia in 1955. (Dripps, R D, Ed: The Physiology of Induced Hypothermia. Washington, D.C., National Academy of Science Publication 451, 1956). These studies established that when cooled, the body's metabolism decreases at about 8% per degree Celsius and drops to one-half the normal at 28° C. Such a reduction in metabolism renders metabolically active organs such as the brain and heart less susceptible to periods of ischemia and hypoxia. As a result of this protective effect, hypothermia is used in heart surgery, brain surgery, spine surgery, aortic surgery, organ transplantation surgery, prevention of cerebral palsy, and treatment of strokes and heart attacks. Despite the expanding role of hypothermia in clinical settings, the methods to induce and maintain hypothermia remain primitive, cumbersome, unpredictable and dangerous.
Cooling the external surface of the body in order to cool the core of the body has been practiced for several centuries. Placing the body in a cold environment, rubbing alcohol on the skin, and placing cold sponges over various parts of the body are still practiced to lower the body temperature. These methods may work to lower fever, but they are unreliable and inefficient to induce hypothermia in a normothermic body. In the 1950's, patients were immersed in iced water to cool and warm water to warm. This involved wheeling full length tubs into the operating room next to the operating table and lowering the patient into the tub, still attached to all the monitoring wires, intravenous lines, arterial lines and breathing tubes. (Churchill-Davidson H C, McMillan I K R, Melrose D C, et al.: Hypothermia: Experimental Study of Surface Cooling. Lancet 2:1011, 1953). This method was dangerous to the patient because of the potential to disconnect intravenous lines, arterial lines, and breathing tubes, aspiration of water, and short-circuiting of monitoring wires. This cooling was cumbersome, erratic and unpredictable. Once the patient was taken out of the cooling tub and placed on the operating table, there was no way to maintain hypothermia because the body reflexively begins to rewarm. The surgeons had to operate quickly or risk damage to heart, brain, and other vital organs.
The limitations of cooling tubs gave rise to cooling blankets. In this method the patient is covered with a blanket that is cooled by circulation of cooled water or other fluid. Cooling of the body occurs slowly and erratically by this method. Ice bags are often placed in the armpits and groin to hasten the cooling process. Access to the patient is difficult with the cooling blanket in place. If the patient needs nursing care, surgical or other procedures to be performed, then the cooling blanket must be removed, resulting in reflex rewarming of the body. In addition to the problems noted in cooling tubs, excessive application of cooling blankets to lower the body temperature to the desired degree could result in frostbite and poor circulation to the limbs.
Extracorporeal cooling involves draining blood out of the body, cooling it to the desired temperature, and pumping it back into the body. Currently, the most effective means of extracorporeal cooling is through cardiopulmonary bypass. In this procedure, the venous blood is taken out of the body, cooled, oxygenated and pumped back into the patient's arterial system. The most common form of extracorporeal circulation used in cardiac and brain surgery involves draining venous blood from the vena cavae and pumping cooled, oxygenated blood into the ascending aorta. If oxygenation is not required and only mild to moderate hypothermia is desired, venous blood may be drained from a peripheral vein, cooled and returned to a peripheral artery.
Cardiopulmonary bypass is a complex procedure involving major thoracic surgery and cannot be maintained for more than a few hours. Some of the potential complications of cardiopulmonary bypass includes pain, surgery, infection, excessive bleeding, aortic dissection, cardiac distension, pericardial tamponade, venous obstruction, brain swelling, brain damage from ischemia and inadequate perfusion, air and clot embolism to brain and other organs, poor oxygenation, retention of carbon dioxide, excessive cooling, depletion of clotting factors and platelets, renal failure, abdominal hemorrhage, ascites, abdominal distention, hypertension, hypotension, and anaphylactoid reaction. In addition, the complex system of tubing, filters, oxygenator, heat exchanger, bubble catcher and the pump are prone to malfunction and breakdown. These limitations make it impossible to maintain cardiopulmonary bypass for more than a few hours, often the duration of a heart or brain operation.
Various forms of cooling devices can be placed inside a vein or an artery to cool the blood as it passes around such device. Cooling of the body with such devices is slow and unpredictable. Surgery is required to place these devices inside a major blood vessel and risk damage to the vessel, bleeding, thrombosis, infection, mechanical obstruction to blood flow, edema, disseminated intravascular coagulation (DIC) and ischemia to distal organs.
In an ischemic event, the blockage results in the death of cells immediately downstream of the blockage within minutes, in a primary cell death area. The dead cells release chemicals that induce collateral blood supplies to be opened in the direction of the primary cell death in an attempt to supply the oxygen-deprived area. The collateral blood openings require time to be formed, too long a time to save the cells in the secondary area using current treatments. Cells in the secondary cell area near the primary area then die in a cascade of cell death. Primary cell death in the brain causes cell expansion within the closed space of the skull, causing a cascade of cell death into secondary areas. The secondary cell death creates more expanding cells and increased pressure within the skull. The increased pressure within the skull reduces blood supply by constricting blood vessels at the very time that increased blood supply is most needed.
The cascade of cell death can greatly increase the size of the infarct region. In cardiac ischemic events, the increased infarct region size can mean an increased area that can later cause arrhythmias, and can lead to heart failure. In brain ischemic events, the increased number of dead cells can mean the difference between a small stroke, and not talking or walking again. What would highly desirable are methods for reducing the cascade of cell death, limiting the damage of heart coronary artery blockages, and limiting the damage caused by strokes. For the reasons earlier described, improved methods and devices for heating and cooling patients would be most advantageous.